DESCRIPTION: Depressive symptoms in schizophrenia, while highly prevalent, often chronic, and disabling, remain relatively understudied. Antidepressants are commonly used in clinical practice to treat a variety of symptoms in patients with schizophrenia. Although some literature describes the treatment of syndromal depression in primarily young adults with schizophrenia, comparatively little research is available to guide the treatment of subsyndromal depressive symptoms in this population, especially in middle-aged and older adults with schizophrenia. Older people with schizophrenia differ from their younger counterparts in several important ways, such as having greater physical comorbidity, cognitive impairment, and a higher risk of side effects. This study will evaluate the efficacy and safety of antidepressant (citalopram) versus placebo augmentation of atypical antipsychotics to treat subsyndromal, residual depressive symptoms in middle-aged and older patients with schizophrenia. This collaborative, two-site (University of California, San Diego and University of Cincinnati), five-year study hypothesizes that citalopram augmentation of antipsychotic medication will be more effective than augmentation with placebo at reducing depressive symptoms and enhancing functioning and quality of life. We propose to enroll a total of 240 outpatients with schizophrenia, who are 55 years or older and have a Hamilton Depression Rating Scale 17-item score of ten or greater, into a randomized, double-blind, flexible-dose, placebo-controlled study. After stabilization for at least four weeks on an atypical antipsychotic agent (either risperidone or olanzapine), patients who have residual depressive symptoms (HAM-D score of ten or greater) will be randomized to one of the following interventions: atypical antipsychotic (risperidone or olanzapine) plus citalopram; or atypical antipsychotic (risperidone or olanzapine) plus placebo. The double-blind treatment period will be three months with a follow-up assessment three months later. Depressive symptoms and side effects will be assessed weekly for the first month, biweekly for the second month, and again at the end of the third month. In addition, we will evaluate cognitive, motor and daily functioning, quality of life, and medication adherence throughout the study. Unique to this proposal, we will use performance-based outcome measures to assess real-world functional capacities. By providing empirical evidence to guide treatment of depressive symptoms in patients with schizophrenia, the study could have significant public health implications for the reduction of disability and the enhancement of quality of life in this patient population.